Large Animal Surgery Resident Oregon State University Corvallis, Oregon
Equine joints affected with osteoarthritis (OA) eventually fail to respond to management. In humans, botulinum neurotoxin type A (BoNT-A) is used to treat refractory joint pain caused by OA. Our goal was to determine effects of BoNT-A on equine articular cartilage. We hypothesized that BoNT-A would ameliorate catabolic and inflammatory effects of interleukin 1 (IL-1) challenge in equine articular cartilage explants and that higher concentrations would have negative effects on normal cartilage. Cartilage explants were obtained from femorotibial joints of 3 cadaver horses with synovial fluid prostaglandin E2 (PGE2) concentrations below 250 pg/ml. Explants from each joint were either challenged with recombinant Equine IL-1 (rEq IL-1) to model osteoarthritic cartilage or unchallenged to represent normal cartilage. Explants were exposed to 1 of 6 concentrations of BoNT-A (0-500 pg/ml). Concentration of PGE2 in culture media was determined via ELISA and release of sulfated glycosaminoglycans (sGAG) from explants into media was measured via DMMB assay. Data was analyzed via 2-way ANOVA (α=0.05). Challenge with rEq IL-1, but not treatment with BoNT-A increased PGE2 concentration in culture media and percentage of sGAG released into the media. BoNT-A did not ameliorate effects of IL-1. This suggests BoNT-A may be safe for intra-articular use, and it is unlikely to be disease modifying. However, the model used for this study only allows for determination of possible BoNT-A disease-modifying effects downstream of IL-1 secretion. Clinical efficacy of intra-articular BoNT-A may be more likely due to analgesic effects.
